Pectolinarigenin and Diosmetin Ameliorate Myocardial Ischemia–Reperfusion Injury by Activating PPARγ/GLUT4 Pathway
6 affiliations
- 1Center for Tissue Engineering and Stem Cell Research, Translation Medicine Research Center, Guizhou Biomanufacturing Laboratory, Guizhou Medical University, Guiyang 561113, China
- 2School of Clinical Medicine, Guizhou Medical University, Guiyang 550025, China
- 3Department of Cardiac Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang 550001, China
- 4Shandong Province Key Laboratory of Detection Technology for Tumor Makers, Linyi University, Linyi 276005, China
- 5State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang 550025, China
- 6Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang 550025, China
Abstract
Background/Objectives: Myocardial ischemia–reperfusion injury (MIRI) is a common complication of thrombolysis, interventional procedures, and bypass surgery, posing a significant threat to patient outcomes. Previous evidence suggests that peroxisome proliferator-activated receptor-γ (PPARγ) agonists can upregulate cardiac glucose transporter 4 (GLUT4) expression after MIRI, thereby enhancing myocardial glucose transport and utilization to improve energy recovery and alleviate injury. This study aimed to screen natural flavonoids for PPARγ agonist activity and to evaluate the cardioprotective effects of the most potent candidates against MIRI. Methods: We assessed 44 natural flavonoids for PPARγ activation using a reporter assay. The selected compounds—diosmetin and pectolinarigenin—were then tested in an isolated perfused heart model of ischemia/reperfusion (I/R) in C57BL/6 mice, measuring infarct size, electrocardiograms, and field potentials. In H9C2 cardiomyocytes subjected to oxygen–glucose deprivation/reoxygenation (OGD/R), we evaluated the release of creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and troponin (Tn). PPARγ and GLUT4 expression were analysed by qPCR and Western blot, and molecular docking was performed to predict binding modes. Results: Both diosmetin and pectolinarigenin exhibited potent PPARγ agonist activity. In isolated hearts, treatment with either compound significantly reduced infarct size and improved electrocardiographic parameters and field potentials compared with the untreated I/R group. In OGD/R-exposed H9C2 cells, both compounds lowered CPK, LDH, and Tn levels. Diosmetin increased GLUT4 protein without significantly altering PPARγ or GLUT4 mRNA, whereas pectolinarigenin increased PPARγ, GLUT4, and total CD36 mRNA and protein in ex vivo hearts. The effects on GLUT4 and CD36 differed between ex vivo hearts and H9C2 cells. Molecular docking revealed that both compounds bind to PPARγ at the interface between helix H3 and the β-sheet. Conclusions: Diosmetin and pectolinarigenin show strong protective effects associated with PPARγ/GLUT4 pathway activation against MIRI in vitro and ex vivo, acting through enhanced GLUT4-mediated glucose metabolism. These flavonoids represent promising lead candidates for further preclinical development in MIRI management.
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BibTeX
@article{wang2026pectolinarigenin,
title = {{Pectolinarigenin and Diosmetin Ameliorate Myocardial Ischemia–Reperfusion Injury by Activating PPARγ/GLUT4 Pathway}},
author = {Yunfei Wang and Jing Zhou and Changhan Ma and Yue Yang and Xiongwei Meng and Min Xu and Jiayu Yu and Dandan Wang and Siyuan Yang and Yadi Zhu and Xingkai Qian},
journal = {Metabolites},
year = {2026},
month = oct,
doi = {10.3390/metabo16110838},
url = {https://www.mdpi.com/2218-1989/16/11/838},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pectolinarigenin and Diosmetin Ameliorate Myocardial Ischemia–Reperfusion Injury by Activating PPARγ/GLUT4 Pathway
AU - Yunfei Wang
AU - Jing Zhou
AU - Changhan Ma
AU - Yue Yang
AU - Xiongwei Meng
AU - Min Xu
AU - Jiayu Yu
AU - Dandan Wang
AU - Siyuan Yang
AU - Yadi Zhu
AU - Xingkai Qian
PY - 2026
DA - 2026/10/31
JO - Metabolites
DO - 10.3390/metabo16110838
UR - https://www.mdpi.com/2218-1989/16/11/838
AB - Background/Objectives: Myocardial ischemia–reperfusion injury (MIRI) is a common complication of thrombolysis, interventional procedures, and bypass surgery, posing a significant threat to patient outcomes. Previous evidence suggests that peroxisome proliferator-activated receptor-γ (PPARγ) agonists can upregulate cardiac glucose transporter 4 (GLUT4) expression after MIRI, thereby enhancing myocardial glucose transport and utilization to improve energy recovery and alleviate injury. This study aimed to screen natural flavonoids for PPARγ agonist activity and to evaluate the cardioprotective effects of the most potent candidates against MIRI. Methods: We assessed 44 natural flavonoids for PPARγ activation using a reporter assay. The selected compounds—diosmetin and pectolinarigenin—were then tested in an isolated perfused heart model of ischemia/reperfusion (I/R) in C57BL/6 mice, measuring infarct size, electrocardiograms, and field potentials. In H9C2 cardiomyocytes subjected to oxygen–glucose deprivation/reoxygenation (OGD/R), we evaluated the release of creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and troponin (Tn). PPARγ and GLUT4 expression were analysed by qPCR and Western blot, and molecular docking was performed to predict binding modes. Results: Both diosmetin and pectolinarigenin exhibited potent PPARγ agonist activity. In isolated hearts, treatment with either compound significantly reduced infarct size and improved electrocardiographic parameters and field potentials compared with the untreated I/R group. In OGD/R-exposed H9C2 cells, both compounds lowered CPK, LDH, and Tn levels. Diosmetin increased GLUT4 protein without significantly altering PPARγ or GLUT4 mRNA, whereas pectolinarigenin increased PPARγ, GLUT4, and total CD36 mRNA and protein in ex vivo hearts. The effects on GLUT4 and CD36 differed between ex vivo hearts and H9C2 cells. Molecular docking revealed that both compounds bind to PPARγ at the interface between helix H3 and the β-sheet. Conclusions: Diosmetin and pectolinarigenin show strong protective effects associated with PPARγ/GLUT4 pathway activation against MIRI in vitro and ex vivo, acting through enhanced GLUT4-mediated glucose metabolism. These flavonoids represent promising lead candidates for further preclinical development in MIRI management.
SN - 2218-1989
ER -